Cholesterol Journal Articles

Record 661 to 680

Amaranth and its oil inhibit cholesterol biosynthesis in 6-week-old female chickens
Qureshi, A. A., J. W. Lehmann, et al. (1996), J Nutr 126(8): 1972-8.
Abstract: All amaranth varieties contain tocotrienols and squalene compounds which are known to affect cholesterol biosynthesis. Therefore, in the present study, the influence of dietary supplementation of whole seed, popped, and milled amaranth and amaranth oil on cholesterogenesis was studied in 6-wk-old female chickens. Serum total cholesterol and LDL-cholesterol were lowered 10-30% and 7-70% (P < 0.01), respectively, in birds fed amaranth-containing diets. HDL-cholesterol was not affected by amaranth supplementation. Activities of liver cholesterol 7alpha-hydroxylase (the enzyme responsible for cholesterol breakdown into bile acids) were 10-18% higher (P < 0.01) than those of controls for birds fed most forms of amaranth and its oil, whereas activities of liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (the rate-limiting enzyme for cholesterol biosynthesis) were lowered by about only 9% (P < 0.01) by popped, milled amaranth and its oil. This lack of marked inhibition of this enzyme suggests the presence of some other potent cholesterol inhibitor(s) apart from tocotrienols and squalene in amaranth.

Amaranth squalene reduces serum and liver lipid levels in rats fed a cholesterol diet
Shin, D. H., H. J. Heo, et al. (2004), Br J Biomed Sci 61(1): 11-4.
Abstract: In this study, the hypocholesterolaemic effect of amaranth grain, oil and squalene are examined. In experiment 1, rats are given a semi-purified diet containing 1% (w/w) cholesterol for four weeks and either amaranth grain (AG; 300 g/kg) or amaranth oil (AO; 90 g/kg) substituted in experimental groups. Both AG and AO lowered serum and hepatic cholesterol and triglyceride levels. Faecal excretion of cholesterol and bile acid in the AO group increased, while AG affected only bile acid excretion. In experiment 2, rats were fed the cholesterol diet for four weeks and injected (i.p.) with saline (control), amaranth squalene (AS) or shark liver squalene (SS, 200 mg/kg) for seven days. The hypolipidaemic effects of AS were evident in both serum and liver. In addition, AS markedly increased faecal excretions of cholesterol and bile acid, and slightly inhibited 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. In contrast, none of these effects were observed in the SS group. This preliminary study suggests that the cholesterol-lowering effect of AS may be mediated by increased faecal elimination of steroids through interference with cholesterol absorption, and that different sources of squalene (plant versus animal) may affect cholesterol metabolism differently.

Amelioration of severity of myocardial injury by a nitric oxide donor in rabbits fed a cholesterol-rich diet
Hoshida, S., M. Nishida, et al. (1996), J Am Coll Cardiol 27(4): 902-9.
Abstract: OBJECTIVES. This study compared the effect of a nitric oxide donor on limiting the size of infarct resulting from myocardial ischemia-reperfusion between atherosclerotic and nonatherosclerotic models. BACKGROUND. Endothelial-derived relaxation in coronary arteries affected by ischemia is substantially impaired after reperfusion, and this impairment may exacerbate the myocardial ischemia-reperfusion injury. In animals with experimental atherosclerosis, release of endothelial-derived relaxing factor is also decreased, and the propagation of myocardial infarction could be exacerbated. METHODS. We examined the extent of myocardial injury induced by ischemia (30 min) and reperfusion (48 hr) in rabbits fed a cholesterol-rich (1%) or normal diet for 10 weeks. We also evaluated the effect of a nitric oxide donor (S-nitroso-N-acetylpenicillamine SNAP, a nitric oxide precursor (L-arginine) or a degradation product of SNAP (N-acetylpenicillamine) on infarct size in these models. RESULTS. Severity of myocardial injury was significantly exacerbated in cholesterol-fed rabbits (75.2 +/- 4.4% mean +/- SEM) compared with that in non-cholesterol-fed rabbits (53.2 +/- 5.2%). This exacerbation was prevented by treatment with SNAP (50.2 +/- 6.4%) but not with L-arginine (70.5 +/- 6.0%) or N-acetylpenicillamine (70.4 +/- 4.8%) in cholesterol-fed-rabbits. However, SNAP did not limit infarct size in non-cholesterol-fed rabbits (60.8 +/- 4.2%). The rate-pressure product was similar during the course of the experiment in all the groups. CONCLUSIONS. Myocardial damage induced by ischemia-reperfusion was significantly exacerbated in rabbits fed a long-term cholesterol-rich diet but was effectively reversed by treatment with a nitric oxide donor. However, this agent did not limit infarct size in normal rabbits. Thus, a nitric oxide donor reduces myocardial infarct size in atherosclerotic but not in nonatherosclerotic rabbits.

American Academy of Pediatrics releases report on cholesterol levels in children and adolescents
Morey, S. S. (1998), Am Fam Physician 57(9): 2266, 2268.

American College of Physicians guidelines on cholesterol screening
Altus, P. (1996), Ann Intern Med 125(12): 1007-8; author reply 1009-10.

American College of Physicians guidelines on cholesterol screening
Fronduti, R. A. (1996), Ann Intern Med 125(12): 1007; author reply 1009-10.

American College of Physicians guidelines on cholesterol screening
Goldstein, M. R. (1996), Ann Intern Med 125(12): 1007; author reply 1009-11.

American College of Physicians guidelines on cholesterol screening
Grundy, S. M. and T. A. Pearson (1996), Ann Intern Med 125(12): 1008; author reply 1009-10.

American College of Physicians guidelines on cholesterol screening
Haq, I. U., P. R. Jackson, et al. (1996), Ann Intern Med 125(12): 1010; author reply 1011.

American College of Physicians guidelines on cholesterol screening
Kryshak, E. J. (1996), Ann Intern Med 125(12): 1008; author reply 1009-10.

American College of Physicians guidelines on cholesterol screening
Ravnskov, U. (1996), Ann Intern Med 125(12): 1010-1.

American College of Physicians guidelines on cholesterol screening
Thacker, H. L. (1996), Ann Intern Med 125(12): 1008-9; author reply 1009-10.

American turnaround in the cholesterol policy
Kristensen, B. O. (1993), Ugeskr Laeger 155(12): 897-9.

Amino acid residue 149 of lecithin:cholesterol acyltransferase determines phospholipase A2 and transacylase fatty acyl specificity
Wang, J., A. K. Gebre, et al. (1997), J Biol Chem 272(1): 280-6.
Abstract: Human LCAT prefers phosphatidylcholine (PC) with sn-1-palmitoyl-2-oleoyl PC (POPC) as substrate for cholesteryl ester synthesis, whereas rat LCAT (which is 92% similar in amino acid sequence) prefers sn-1-palmitoyl-2-arachidonoyl PC (PAPC). Six recombinant human LCAT cDNA clones were constructed with unique clusters of rat sequence substitutions in the human background spanning the region encoding amino acids 121-296. Media from transfected COS cells expressing each of the constructs were assayed for LCAT cholesterol esterification (CE) or phospholipase A2 (PLA2) activity using substrate particles containing POPC or PAPC. The PAPC/POPC CE activity ratio of the cluster 1 construct (amino acids 149-158) was 1.3, resembling rat LCAT, whereas cluster 2-5 clones produced CE activity ratios <0.3, unchanged from human LCAT. The cluster 6 clone (Y292H/W294F) had an intermediate ratio (0.6). Similar results were observed for LCAT PLA2 activity. In additional studies, position 149 of human LCAT was changed to the rat sequence (hE149A) and compared to a triple mutation containing the remainder of the cluster 1 changes (G151R/E154D/R158Q). CE and PLA2 activity ratio for the hE149A construct was >1.7, similar to rat LCAT, whereas the triple mutation construct retained a ratio similar to human LCAT (<0.6). Thus, a single amino acid substitution (E149A) was sufficient to alter the fatty acyl specificity of human LCAT to that of rat LCAT, with an increase in activity toward PAPC. This is the first example of a point mutation in an enzyme with PLA2 activity that results in an increase in activity toward arachidonic acid.

Amino acids and cholesterol levels of leukemic lymphocytes infected with bovine leukemia virus (BLV)
Madej, J. A., S. Klimentowski, et al. (1992), Arch Vet Pol 32(3-4): 27-33.
Abstract: We performed qualitative and quantitative amino acids analysis of lymphocytes from normal and leukemic cattle (infected with bovine leukemia virus) to determine cellular cholesterol levels. Leukemic lymphocytes exhibited quantitative differences in the levels of some "glycogenic", "ketogenic" and "glyco-ketogenic" amino acids. These differences may reflect the disturbances of Krebs cycle. Evidence was produced that increased cholesterol content in the above lymphocytes was associated with disorders in beta-oxidation processes of leukemic cells.

Amino terminal 38.9% of apolipoprotein B-100 is sufficient to support cholesterol-rich lipoprotein production and atherosclerosis
Chen, Z., R. L. Fitzgerald, et al. (2003), Arterioscler Thromb Vasc Biol 23(4): 668-74.
Abstract: OBJECTIVE: Carboxyl terminal truncation of apolipoprotein (apo)B-100 and apoB-48 impairs their capacity for triglyceride transport, but the ability of the resultant truncated apoB to transport cholesterol and to support atherosclerosis has not been adequately studied. The atherogenicity of apoB-38.9 was determined in this study by using our apoB-38.9-only (Apob38.9/38.9) mice. METHODS AND RESULTS: ApoB-38.9-lipoproteins (Lp-B38.9) circulate at very low levels in Apob38.9/38.9 mice as small LDLs or HDLs. Disruption of apoE gene in these mice caused accumulation of large amounts of betaVLDL-like LpB-38.9 in plasma. These betaVLDL particles were more enriched with cholesteryl esters but poor in triglycerides compared with the apoB-48-betaVLDL of the apoB-wild-type/apoE-null (Apob+/+/Apoe-/-) mice. Likewise, apoB-38.9-VLDL secreted by cultured Apob38.9/38.9 mouse hepatocytes also had higher ratios of total cholesterol to triglycerides than apoB-48-VLDL secreted by the apoB-48-only hepatocytes. Thus, despite its impaired triglyceride-transporting capacity, apoB-38.9 has a relatively intact capacity for cholesterol transport. Spontaneous aortic atherosclerotic lesions were examined in apoB-38.9-only/apoE-null (Apob38.9/38.9/Apoe-/-) mice at ages 9 and 13 months. Extensive lesions were found in the Apob38.9/38.9/Apoe-/- mice as well as in their Apob+/38.9/Apoe-/- and Apob+/+/Apoe-/- littermates. CONCLUSIONS: Deleting the C-terminal 20% from apoB-48 does not impair its ability to transport cholesterol and to support atherosclerosis, thus narrowing the "atherogenic region" of apoB.

Amino terminal region of acute phase, but not constitutive, serum amyloid A (apoSAA) specifically binds and transports cholesterol into aortic smooth muscle and HepG2 cells
Liang, J. S., B. M. Schreiber, et al. (1996), J Lipid Res 37(10): 2109-16.
Abstract: The human apoSAA proteins comprise both acute phase (apoSAA1, apoSAA2) and constitutive (apoSAA4) isoforms; all are expressed in human atherosclerotic lesions as well as in liver. Recombinant acute phase apoSAA binds cholesterol with an affinity of approximately 170 nM and enhances cholesterol uptake by HepG2 cells (J. Lipid Res. 1995. 36:37-46). In the present study, we sought to define the region of acute phase apoSAA involved in cholesterol binding and to investigate the ability of constitutive apoSAA4 to bind cholesterol. Binding of 3Hcholesterol to apoSAAp was inhibited by unlabeled cholesterol (1-100 nM), but not significantly by vitamin D and estradiol. Direct binding of acute phase, but not constitutive, apoSAA to the surfaces of polystyrene microtiter wells was strongly diminished in the presence of cholesterol. The ability of apoSAAp to bind cholesterol was inhibited by antibodies to human apoSAA1 and to peptide 1-18 of apoSAA1. There was only slight inhibition of cholesterol binding by antibodies to peptide 40-63, and no inhibition by antibodies to peptides spanning regions containing amino acid residues 14-44 and 59-104. 3Hcholesterol uptake by neonatal rabbit aortic smooth muscle and HepG2 cells was enhanced by a synthetic peptide corresponding to amino acids 1-18 of hSAA1, but not by peptides corresponding to amino acids 1-18 of hSAA4. 3Hcholesterol uptake by HepG2 cells was slightly increased by a peptide corresponding to amino acids 40-63 of hSAA1. These findings suggest that apoSAA modulates the local flux of cholesterol between cells and lipoproteins during inflammation and atherosclerosis.

Aminoguanidine has an anti-atherogenic effect in the cholesterol-fed rabbit
Panagiotopoulos, S., R. C. O'Brien, et al. (1998), Atherosclerosis 136(1): 125-31.
Abstract: Advanced glycosylation endproducts (AGEs) which result from the non-enzymatic interaction of proteins and glucose are implicated in the vasculopathy of diabetes and aging. Since aminoguanidine (A) inhibits the accumulation of AGEs, we explored its effects on the development of atherosclerosis. Male New Zealand white cross rabbits fed a high cholesterol (1%) diet were randomized to control (C) or increasing doses of A treatment (25, 50 and 100 mg/kg A body weight). The animals were sacrificed after 12 weeks. Sudan IV was used to stain the lipid containing plaques of the aortic arch, thoracic and abdominal aorta and the surface area occupied by atheroma was assessed. Increasing doses of A treatment were associated with reduction in plaque formation in the aorta. At a dose of 100 mg/kg A, there was a 30, 49 and 48% reduction in plaque formation in the aortic arch, thoracic and abdominal aorta, respectively. There was a correlation between AGE levels and the degree of atheroma in these cholesterol fed rabbits (control, r = 0.75, P < 0.01; 100 mg/kg A, r = 0.59, P = 0.02). These data suggest that advanced glycation may participate in atherogenesis and raise the possibility that inhibitors of advanced glycation may retard this process.

Aminopeptidase N (CD13) is a molecular target of the cholesterol absorption inhibitor ezetimibe in the enterocyte brush border membrane
Kramer, W., F. Girbig, et al. (2005), J Biol Chem 280(2): 1306-20.
Abstract: Intestinal cholesterol absorption is an important regulator of serum cholesterol levels. Ezetimibe is a specific inhibitor of intestinal cholesterol absorption recently introduced into medical practice; its mechanism of action, however, is still unknown. Ezetimibe neither influences the release of cholesterol from mixed micelles in the gut lumen nor the transfer of cholesterol to the enterocyte brush border membrane. With membrane-impermeable Ezetimibe analogues we could demonstrate that binding of cholesterol absorption inhibitors to the brush border membrane of small intestinal enterocytes from the gut lumen is sufficient for inhibition of cholesterol absorption. A 145-kDa integral membrane protein was identified as the molecular target for cholesterol absorption inhibitors in the enterocyte brush border membrane by photoaffinity labeling with photoreactive Ezetimibe analogues (Kramer, W., Glombik, H., Petry, S., Heuer, H., Schafer, H. L., Wendler, W., Corsiero, D., Girbig, F., and Weyland, C. (2000) FEBS Lett. 487, 293-297). The 145-kDa Ezetimibe-binding protein was purified by three different methods and sequencing revealed its identity with the membrane-bound ectoenzyme aminopeptidase N ((alanyl)aminopeptidase; EC 3.4.11.2; APN; leukemia antigen CD13). The enzymatic activity of APN was not influenced by Ezetimibe (analogues). The uptake of cholesterol delivered by mixed micelles by confluent CaCo-2 cells was partially inhibited by Ezetimibe and nonabsorbable Ezetimibe analogues. Preincubation of confluent CaCo-2 cells with Ezetimibe led to a strong decrease of fluorescent APN staining with a monoclonal antibody in the plasma membrane. Independent on its enzymatic activity, aminopeptidase N is involved in endocytotic processes like the uptake of viruses. Our findings suggest that binding of Ezetimibe to APN from the lumen of the small intestine blocks endocytosis of cholesterol-rich membrane microdomains, thereby limiting intestinal cholesterol absorption.

Amiodarone induces a dose-dependent increase of plasma cholesterol in the rat
Wiersinga, W. M. and M. Broenink (1991), Horm Metab Res 23(2): 94-5.

Cholesterol Articles and Abstracts

Cholesterol Journal Articles